Foxp3 regulates megakaryopoiesis and platelet function.
Foxp3 regulates megakaryopoiesis and platelet function.
Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1874-82
Authors: Bernard JJ, Seweryniak KE, Koniski AD, Spinelli SL, Blumberg N, Francis CW, Taubman MB, Palis J, Phipps RP
OBJECTIVE: Platelets are crucial for hemostasis and are vital regulators of inflammation. Foxp3 is a key transcription factor for T regulatory cell development. Humans with IPEX (immune dysregulation, polyendocrinopathy, enteropathy, x-linked) and the scurfy (Foxp3(sf)) mouse have mutations in the Foxp3 gene that lead to a host of pathologies including autoimmunity and skin diseases. Scurfy mice and some humans with IPEX are also thrombocytopenic. The purpose of this study was to determine whether the absence of functional Foxp3 leads to defects in megakaryocytes and platelets. METHODS AND RESULTS: We discovered that human and mouse megakaryocytes express Foxp3 mRNA and protein. Using shRNA and Foxp3(sf) mice, we demonstrated that Foxp3-deficient mouse and human megakaryocyte progenitors exhibited proliferation defects. Striking platelet abnormalities were observed in both an IPEX patient and Foxp3(sf) mice. Impaired platelet spreading and release of TGF-beta and CD40 ligand (CD40L), and abnormal levels of plasma CD40L were observed in a case of IPEX syndrome. Foxp3(sf) mice were thrombocytopenic and had increased platelet volume and altered serum levels of CD40L, TXB(2), and TGF-beta. CONCLUSIONS: These findings provide compelling new evidence that Foxp3 is needed for proper megakaryopoiesis and plays a role in regulating platelet function including spreading and release.
PMID: 19661482 [PubMed - indexed for MEDLINE]
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Posted in: Arterioscler Thromb Vasc Biol
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on Friday, February 5th, 2010 at 2:19 pm and is filed under Arterioscler Thromb Vasc Biol.
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Foxp3 regulates megakaryopoiesis and platelet function.
Foxp3 regulates megakaryopoiesis and platelet function.
Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1874-82
Authors: Bernard JJ, Seweryniak KE, Koniski AD, Spinelli SL, Blumberg N, Francis CW, Taubman MB, Palis J, Phipps RP
OBJECTIVE: Platelets are crucial for hemostasis and are vital regulators of inflammation. Foxp3 is a key transcription factor for T regulatory cell development. Humans with IPEX (immune dysregulation, polyendocrinopathy, enteropathy, x-linked) and the scurfy (Foxp3(sf)) mouse have mutations in the Foxp3 gene that lead to a host of pathologies including autoimmunity and skin diseases. Scurfy mice and some humans with IPEX are also thrombocytopenic. The purpose of this study was to determine whether the absence of functional Foxp3 leads to defects in megakaryocytes and platelets. METHODS AND RESULTS: We discovered that human and mouse megakaryocytes express Foxp3 mRNA and protein. Using shRNA and Foxp3(sf) mice, we demonstrated that Foxp3-deficient mouse and human megakaryocyte progenitors exhibited proliferation defects. Striking platelet abnormalities were observed in both an IPEX patient and Foxp3(sf) mice. Impaired platelet spreading and release of TGF-beta and CD40 ligand (CD40L), and abnormal levels of plasma CD40L were observed in a case of IPEX syndrome. Foxp3(sf) mice were thrombocytopenic and had increased platelet volume and altered serum levels of CD40L, TXB(2), and TGF-beta. CONCLUSIONS: These findings provide compelling new evidence that Foxp3 is needed for proper megakaryopoiesis and plays a role in regulating platelet function including spreading and release.
PMID: 19661482 [PubMed - indexed for MEDLINE]
Sponsored Content:
Posted in: Arterioscler Thromb Vasc Biol
This entry was posted
on Friday, February 5th, 2010 at 2:19 pm and is filed under Arterioscler Thromb Vasc Biol.
You can follow any responses to this entry through the RSS 2.0 feed.
You can skip to the end and leave a response. Pinging is currently not allowed.
